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Purpose A meta-analysis is presented comparing the overall survival (OS) and local control (LC) rates between penectomy and brachytherapy for penile cancer. Methods and materials A PUBMED search was conducted with the MeSH terms, “penis, penile, cancer, brachytherapy, penectomy, surgery, treatment” in various combinations. Nineteen retrospective studies published between the years 1984–2012, detailing OS and LC were included. Data were collected per Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Results A total of 2178 males, median age 61 years, were included with 1505 in the surgery group and 673 in the brachytherapy group. The 5-year OS with surgery was 76% compared with 73% with brachytherapy, odds ratio = 1.17 (0.95–1.44, p = 0.128). Penectomy was associated with a higher 5-year LC rate of 84% compared with 79% with brachytherapy, odds ratio = 1.45 (1.09–1.92, p = 0.009). The organ preservation rate for brachytherapy treatment was 74%. Among the surgery patients in a Stage I/II subset, the 5-year OS and LC was 80% (n = 659) and 86% (n = 390), respectively. Of the 209 early stage patients who received brachytherapy, the 5-year OS was 79% and LC was 84%. Chi-square testing demonstrated no difference for either OS or LC for early stage disease. Conclusions This meta-analysis is limited by the retrospective nature and inherent selection bias of the data. While penectomy provided better control, there was no survival benefit, implying that in most cases failed brachytherapy could be salvaged with surgery. Additionally, in early stage tumors there was no survival or control difference.

Purpose High-dose-rate (HDR) brachytherapy boost in prostate cancer allows dose escalation and delivery of higher biologically effective dose (BED). We evaluated the outcomes of intensity-modulated radiation therapy (IMRT) and HDR boost in a community setting. Methods and Materials Between July 2003 and April 2008, 148 patients with prostate cancer were treated at Cancer Center of Irvine using two transperineal implants performed 1 week apart (22 Gy delivered in four fractions divided between two insertions and delivered twice daily), followed by IMRT (50.4 Gy). Hormonal therapy was given for 1 year to all patients with Gleason score of 8 or higher. Results Patient characteristics are as follows: median age at treatment, 71 years; American Joint Committee on Cancer Group IIB, 53%; Gleason score of 7, 41%; and Gleason score of 8 or higher, 14%. Median followup was 49 months, and median prostate-specific antigen (PSA) nadir was 0.15 ng/mL. The 4-year actuarial biochemical disease-free survival (bDFS) was 96.8/81% by Phoenix/PSA lower than 0.5 ng/mL criteria. According to National Comprehensive Cancer Center Clinical Practice Guidelines–defined recurrence risk groups, 4-year bDFS for low risk was 100/92.9%, intermediate risk was 100/86.7%, and high risk was 94/75.4% by Phoenix/PSA lower than 0.5 ng/mL criteria. No statistically significant difference in bDFS was detected by either failure criteria based on risk group, lymph node risk, or initial PSA. Treatment was well tolerated. Subacute/late genitourinary and gastrointestinal toxicities were limited to 10% and 5%, respectively of all patients. Conclusions Prostate IMRT plus HDR brachytherapy boost was well tolerated with appropriate PSA response and bDFS at 4 years, demonstrated in a community setting. This treatment schema provides a high BED, comparable with hypofractionated prostate regimens previously reported in the literature. Higher BED delivery should be explored in further dose escalation studies.

Purpose To evaluate the clinical utility of capromab pendetide imaging with single photon emission computed tomography coregistration with computed tomography (SPECT/CT) in primary prostate cancer (CaP) for pretreatment prognostic staging and localization of biologic target volumes (BTV) for individualized image-guided radiotherapy dose escalation (IGRT-DE). Methods and Materials Patients consecutively presenting for primary radiotherapy (February 1997 to December 2002), having a clinical diagnosis of localized CaP, were evaluated for tumor stage using conventional staging and SPECT/CT ( N = 239). Distant metastatic uptake (mets) were identified by SPECT/CT in 22 (9.2%). None of the suspected mets could be clinically confirmed. Thus, all subjects were followed without alteration in disease management. The SPECT/CT pelvic images defined BTV for IGRT-DE (+150% brachytherapy dose) without ( n = 150) or with ( n = 89) external radiation of 45 Gy. The National Comprehensive Cancer Network criteria defined risk groups (RG). The median survivor follow-up was 7 years. Biochemical disease-free survival (bDFS) was reported by clinical nadir +2 ng/mL (CN+2) criteria. Statistical analyses included Kaplan-Meier, multivariate analysis, and Concordance-index models. Results At 10-year analyses, overall survival was 84.8% and bDFS was 84.6%. With stratification by RG, CN+2 bDFS was 93.5% for the low-RG ( n = 116), 78.7% for the intermediate-RG ( n = 94), and 68.8% for the high-RG ( n = 29), p = 0.0002. With stratification by pretreatment SPECT/CT findings, bDFS was 65.5% in patients with suspected mets ( n = 22) vs. 86.6% in patients with only localized uptake ( n = 217), p = 0.0014. CaP disease-specific survival (DSS) was 97.7% for the cohort. With stratification by SPECT/CT findings, DSS was 86.4% (with suspected mets) vs. 99.0% (localized only), p = 0.0001. Using multivariate analysis, the DSS hazard ratio for SPECT/CT findings (mets vs. localized) was 3.58 ( p = 0.0026). Concordance-index tests, based on all data, by CN+2 bDFS criteria were 0.710 for RG alone and 0.773 for SPECT/CT + RG. Conclusions Through long-term outcomes we demonstrate statistically significant bDFS and DSS predictive value for pretreatment capromab pendetide SPECT/CT imaging in primary CaP. Dual clinical utility is demonstrated, using SPECT/CT to define BTV for individualized IGRT-DE.

Purpose: We evaluate the usefulness of pretreatment 111Indium capromab pendetide (ProstaScint™) planar imaging (immunoscintigraphy) plus single photon emission tomography co-registration with computerized tomography scans to detect occult metastatic disease and predict for biochemical failure, in a cohort of patients with a clinical diagnosis of localized adenocarcinoma of the prostate referred for primary radiotherapy.Materials and Methods: Patients were followed after radiotherapy for evidence of biochemical failure using 2 criteria of prostate specific antigen clinical nadir +2 ng/ml and American Society for Therapeutic Radiology and Oncology Consensus definitions. Median followup was 58.8 months (mean 64.8). Clinical risk factors defined 3 risk groups of high (51), intermediate (72) and low (116).Results: Overall biochemical failure was 18.3% vs 11.8% by the 2-BFC at 8-year actuarial analysis with 58.8 months median followup. By the CN +2 definition the control date for the cohort is 34.8 months. Pret...

Purpose To evaluate rectal morbidity after dose escalation to biologic target volumes identified by capromab pendetide (ProstaScint) single-photon emission tomography images coregistered with computed tomography (SPECT/CT). Methods and materials Two hundred thirty-nine consecutive patients diagnosed with T1c–T3b NxM0 adenocarcinoma of the prostate were treated with brachytherapy seed implant (SI) dose escalation to SPECT/CT–identified biologic target volumes, from February 1997 through December 2002. Patients received SI (n = 150) or external beam radiation therapy plus SI (n = 89). Rectal morbidity was evaluated by clinician scoring using the modified Radiation Therapy Oncology Group criteria. The median followup was 47.2 (range 24.8–96.1) months. Results The rate of acute Grades I and II toxicity was 29.9% and 3.7%, respectively, and chronic Grade I toxicity was 15.4%, 12.4%, 2.3%, and 1.8% at 1, 2, 3, and 4 years postimplant, respectively. Chronic Grade II toxicities were 1.8%, 1.9%, 1.5%, and 0.9% at 1, 2, 3, and 4 years, respectively. No Grade III rectal toxicity was reported. Chronic Grade IV rectal toxicity was 0.5% and 0.6% at 1.5 and 2.5 years, respectively. Ninety-six percent of patients reported freedom from all rectal toxicity after 3 years. Conclusions Dose intensification to occult tumor targets without increasing rectal toxicity may be achieved using SPECT/CT ProstaScint. Additional research to define the role of molecular imaging in prostate cancer is warranted.

Purpose To report biochemical disease-free survival (bDFS) after conformal brachytherapy with dose escalation to biological target volumes (BTVs) identified by Capromab Pendetide with single photon emission computed tomography and computed tomography image fusion (SPECT/CT). Methods and materials Two hundred thirty-nine (T1c–T3b NxM0) consecutive patients were evaluated by SPECT/CT before treatment. Intraprostatic SPECT/CT BTVs were identified and targeted for 150% dose escalation during brachytherapy seed implant (SI). Patients received either SI alone ( n = 150) or external beam radiation therapy (EBRT) plus SI boost (EBRT + SI) ( n = 89), with ( n = 50) and without ( n = 189) neoadjuvant hormone ablation therapy. Risk factors (RF) (prostate-specific antigen [PSA] >10 ng/mL, Stage ≥T2b, and Gleason grade ≥7) defined risk group (RG) categories [none, 1, and ≥2 RF define low, intermediate, and high RG] for bDFS calculations using four failure criteria: American Society for Therapeutic Radiology and Oncology (ASTRO) consensus definition, PSA >1.0 ng/mL (PSA >1), PSA >0.5 ng/mL after nadir (PSA >0.5), and PSA nadir + 2 ng/mL rise in PSA clinical nadir (CN + 2). Median followup was 47.2 months (range, 24.8–96.1). Results Seven-year actuarial bDFS rates were 88.0%, 82.1%, 80.4%, and 79.9% using the ASTRO, PSA >1, PSA >0.5, and CN + 2 failure criteria, respectively. ASTRO-defined bDFS rates were 96.0%, 87.0%, and 72.5% for low, intermediate, and high RG's. Conclusion The data presented here demonstrate the feasibility of performing SPECT/CT BTV dose escalation in a mature series.

Advances in imaging technologies, including computerized tomography (CT) and single-photon emission tomography (SPECT), are improving the role of imaging in prostate cancer diagnosis and treatment. Hybrid (SPECT/CT) imaging, in particular, shows an increased sensitivity for identification of prostate cancer. Published studies have also recently proposed a new paradigm in the administration of radiation therapy for prostate cancer, favoring dose-escalation strategies to improve tumor control for localized disease. Conventional dose-escalation protocols have previously relied primarily on margin extension to the entire prostate gland to achieve dose-escalation; extending increased risk to radiosensitive normal structures. A newer strategy proposes use of advanced imaging to confine dose-escalation to biological target volumes identified on capromab pendetide SPECT/CT -fused image sets or image-guided radiation therapy (IGRT). This strategy defines a shift in radiation dosimetry and planning from uniform glandular prescription dosing with dose-escalation applied generically to the peripheral regions and margin extension; to dose-escalation confinement to discrete regions of known disease as defined by focal uptake on radioimmunoscintigraphy fusion with anatomic image sets, with minimal margin extension. The introduction of advanced imaging for IGRT in prostate cancer has also introduced an improved capability for the early-identification of patients at risk for metastatic disease, where more aggressive therapeutic interventions may prove beneficial.

treatments using BED 5 nd [1þ (d/a/b)] and for low-dose-rate I125 or Pd103 BED 5 (R0/l) {1þ[R0 ⁄(mþl)(a/b)]} a/b of 1.86 and 3 Gy were applied for prostate cancer and normal tissue respectively. The BED values for treatments involving both implant and EBRT were calculated by adding the BEDs computed for each treatment. Heterogeneity correction for the seeds was applied to determine the impact of seeds on dose computation. Results: The computed BED via I125 alone were 112Gya/b51.86 and 110 Gya/b53 for prostate and normal tissue, respectively while via Pd103 alone were 111 Gya/b 51.86 and 108 Gya/b53, respectively. The total dose delivered via I125 and Pd103 alone was 85 and 82 Gy, respectively. The total dose delivered from I125 SIBB þ EBRT were 175Gya/b51.86 and 136 Gy a/b53 to prostate and normal tissue, respectively. While Pd103 SIBB þ EBRT doses were 185 Gya/b51.86 and 144 Gya/b 5 3 to prostate and normal tissue, respectively. Inclusion of I125 and Pd103 SIBB resulted in approximately 25% and 20% increase in prostate and normal tissue doses, respectively. Heterogeneity correction for the seeds showed minor impact ( 5%) on EBRT dose computation. Conclusions: Integrating the SSIB and EBRT should be utilized with caution as it delivers significant extra-dose to the prostate and normal tissues. Heterogeneity correction for the seeds seems to be of minor impact on dose computation.

Purpose: To evaluate an IGART scheme for prostate cancer that uses deformable CBCT image registration to track daily delivered dose (accumulated over time) to targets and organs‐at‐risk and allows comparison to the original treatment plan. Methods: Six patients treated with external beam radiation therapy for high risk prostate cancer were evaluated. Daily CBCTs were obtained for setup evaluation for all 45 fractions. Contours were transferred from the planning CT to the Day 1 CBCT to serve as the surrogate planning CT for deformation. Dose was applied automatically to each CBCT based on the recorded shift for that day. The daily CBCTs were deformed back to the first CBCT to sum the dose over the course of treatment. Contours were also deformed from the Day 1 CBCT to each subsequent day to allow for daily DVH evaluation. The accumulated delivered dose (summed from each daily treatment) and the planned dose were compared in terms of min, mean, max doses to structures: bladder, rectum, and PTV. Results: The average percentage differences between planned and delivered doses were: bladder — Dmin (8.2 +/− 13.4), Dmean (7.3 +/− 12.7), Dmax (−4.2 +/− 2.7); rectum — Dmin (−16.4 +/−41.4), Dmean (0.8 +/−9.8), Dmax (−3.2 +/−2.3); PTV — Dmin (−16.7 +/− 12.9), Dmean (−3.8 +/−2.7), Dmax (−4.1 +/− 2.9). Conclusion: An IGART scheme for prostate cancer using daily CBCTs and deformable registration was evaluated and found to be feasible. Further work is planned using a larger cohort of patients to evaluate the impact of dose differences between planned and delivered doses. Aaron Nelson and Jonathon Piper are owners and employees of MIM Software Inc. Sara Pirozzi, Ian Liu, and Zhilei Shen are employees of MIM Software Inc.

Stereotactic Radiosurgery for Renal Cancer: Phase I Safety and Toxicity R.J. Ellis, R.B. Patel, C. Kunos, Y. Zhang, J. Brindle, V. Kudithipudi, D.A. Kaminsky, and L. Ponsky; University Hospitals Seidman Cancer Center, Department of Radiation Oncology, Cleveland, OH, Case Western Reserve University Medical School, Cleveland, OH, Northeastern Ohio University College of Medicine, Rootstown, OH, University Hospitals Seidman Cancer Center, Department of Urology, Cleveland, OH

Purpose: To evaluate a deformable contouring method for prostate CBCT as part of an automated image‐guided adaptive radiation therapy (IGART) workflow using manual contours from multiple observers for comparison. Methods: Three CBCTs were randomly selected from 6 patients with prostate cancer. Prostate, bladder, and rectum contours were manually defined on the first CBCT by a single observer and on the second and third CBCTs by 3 observers. A commercial free‐form intensity based deformable contouring method was used to deform contours from the first CBCT to the second and third CBCTs. The Dice coefficients and the absolute differences in measured daily delivered dose values were calculated among the deformed and manual contours. Two‐sided t‐tests were performed to determine whether the automated deformable method has similar variability to manual contours from multiple observers. Results: The mean(SD) Dice coefficients calculated between the deformed contours and each of the manual contours were 0.72(0.10), 0.75(0.13), 0.64(0.10) for the prostate, bladder, and rectum, respectively, and were 0.76(0.08), 0.87(0.05), 0.68(0.10), respectively, averaged between multiple observer comparisons. These differences were not significant for the rectum (p=0.095) but were significant for the prostate (p=0.025) and bladder (p 0.05). The difference was significant for the bladder (p